Synthesis of Highly Enantioenriched Sulfonimidoyl Fluorides and Sulfonimidamides by Stereospecific Sulfur–Fluorine Exchange (SuFEx) Reaction

Sulfonimidamides present exciting opportunities as chiral isosteres of sulfonamides, with potential for additional directional interactions. Here, we present the first modular enantioselective synthesis of sulfonimidamides, including the first stereoselective synthesis of enantioenriched sulfonimidoyl fluorides, and studies on their reactivity. A new route to sulfonimidoyl fluorides is presented from solid bench-stable, N-Boc-sulfinamide (Boc=tert-butyloxycarbonyl) salt building blocks. Enantioenriched arylsulfonimidoyl fluorides are shown to be readily racemised by fluoride ions. Conditions are developed, which trap fluoride and enable the stereospecific reaction of sulfonimidoyl fluorides with primary and secondary amines (100 % es, es=enantiospecificity) generating sulfonimidamides with up to 99 % ee. Aryl and alkyl sulfonimidoyl fluoride reagents are suitable for mild late stage functionalisation reactions, exemplified by coupling with a selection of complex amines in marketed drugs.     

Cross-coupling of alkynylsilanols with aryl halides promoted by potassium trimethylsilanolate

The palladium-catalyzed cross-coupling of aliphatic alkynylsilanols with aryl iodides has been demonstrated with potassium trimethylsilanolate as the coupling promoter and copper(I) iodide as a cocatalyst. The cross-coupling proceeds at room temperature in good to excellent yield with a range of aryl iodides. A comparison of the reactivity of alkynylsilanols, trimethylsilylalkynes, and terminal alkynes under fluoride and fluoride-free conditions was performed to elucidate the role of silicon in the Sonogashira reaction.     

Stille cross-coupling of activated alkyltin reagents under "ligandless" conditions

Monoalkyltins activated by a fluoride source are shown to be as reactive as their vinyl or aryl homologues in the Stille coupling reaction, thus providing an easy entry into the pallado-catalyzed formation of Csp3-Csp2 bonds. In addition to this uncommon reactivity, this methodology holds several advantages such as (i) a quantitative preparation of stable and easy to handle alkyltin reagents 2, (ii) a simplified coupling procedure without any phosphine added ligand under neutral conditions, and (iii) a facile purification step of the organic products from the inorganic nontoxic tin byproducts.     

Chemical reactivity assay and surface characterization of a poly(vinylidene fluoride) microfiltration membrane (“Durapore DVPP”)

Surface functionalization of a commercially available poly(vinylidene fluoride) (PVDF) filtration membrane (Millipore DVPP) was performed using organic synthesis at the solid–liquid interface. Hydroxyl groups present on this hydrophilic membrane were activated by reaction with several activating and coupling agents prior to the covalent grafting of lysine. Transamination was used as well as a grafting method. The apparent surface of the PVDF membrane was characterized using SEM and XPS techniques before and after the wet chemical treatments. On the other hand, chemical reactivity of the open surface was assayed by the coupling to tritiated lysine and liquid scintillation counting (LSC) of the radioactivity associated to the samples.     

Palladium‐Catalyzed Defluorinative Coupling of 1‐Aryl‐2,2‐Difluoroalkenes and Boronic Acids: Stereoselective Synthesis of Monofluorostilbenes

The palladium‐catalyzed defluorinative coupling of 1‐aryl‐2,2‐difluoroalkenes with boronic acids is described. Broad functional‐group tolerance arises from a redox‐neutral process by a palladium(II) active species which is proposed to undergo a β‐fluoride elimination to afford the products. The monofluorostilbene products were formed with excellent diastereoselectivity (≥50:1) in all cases, and it is critical, as traditional chromatographic techniques often fail to separate monofluoroalkene isomers. As a demonstration of this method's unique combination of reactivity and functional‐group tolerance, a Gleevec® analogue, using a monofluorostilbene as an amide isostere, was synthesized.     

Reactivity of acid fluoride-terminated self-assembled monolayers on gold

This report describes the reactivity of acid fluoride (AF)-terminated self-assembled monolayers (SAMs) on gold toward amine and alcohol compounds and the potentiality of AF as a reactive intermediate for surface functionalizations. The AF group was generated in situ on a gold surface by reacting the terminal carboxylic acid group in the SAM of 16-mercaptohexadecanoic acid with cyanuric fluoride and pyridine under the optimized conditions. AF was found to be highly reactive toward various amine groups, such as primary and secondary amines, but it did not react effectively with alcohol. In addition, the amide coupling reaction by microcontact printing (microCP) was compared with the solution-based reaction: when amine-derivatized ferrocene compound was used for 1-min microCP on the AF-activated surface, the surface coverage of the reaction product was about 83% of 3.45 x 1014 cm-2, the coverage obtained in the solution-based reaction. On the basis of the high reaction efficiency of microCP, the AF-activated surface was also used as a platform for patterning a biological ligand, biotin.     

Suzuki–Miyaura Coupling of (Hetero)Aryl Sulfones: Complementary Reactivity Enables Iterative Polyaryl Synthesis

Ideal organic syntheses involve the rapid construction of C?C bonds, with minimal use of functional group interconversions. The Suzuki–Miyaura cross‐coupling (SMC) is a powerful way to form biaryl linkages, but the relatively similar reactivity of electrophilic partners makes iterative syntheses involving more than two sequential coupling events difficult to achieve without additional manipulations. Here we introduce (hetero)aryl sulfones as electrophilic coupling partners for the SMC reaction, which display an intermediate reactivity between those of typical aryl (pseudo)halides and nitroarenes. The new complementary reactivity allows for rapid sequential cross‐coupling of arenes bearing chloride, sulfone and nitro leaving groups, affording non‐symmetric ter‐ and quateraryls in only 2 or 3 steps, respectively. The SMC reactivity of (hetero)aryl sulfones is demonstrated in over 30 examples. Mechanistic experiments and DFT calculations are consistent with oxidative addition into the sulfone C?S bond as the turnover‐limiting step. The further development of electrophilic cross‐coupling partners with complementary reactivity may open new possibilities for divergent iterative synthesis starting from small pools of polyfunctionalized arenes.     

Utilization of Tetrabutylammonium Triphenyldifluorosilicate as a Fluoride Source for Silicon-Carbon Bond Cleavage

Tetrabutylammonium triphenyldifluorosilicate (TBAT) can be employed as a fluoride source to cleave silicon-carbon bonds thus generating in situ carbanions that coupled with a variety of electrophiles, including aldehydes and ketones, in moderate to high yields. Among the examples reported is the first instance of fluoride-induced intermolecular coupling between allyltrimethylsilane and imine derivatives. Also, of particular note is the TBAT-initiated coupling of primary alkyl halides with allyltrimethylsilane. TBAT is an easily handled crystalline solid that has several advantages over tetrabutylammonium fluoride (TBAF) as a fluoride source; it is anhydrous, nonhygroscopic, soluble in most commonly used organic solvents, and less basic than TBAF.     

Vinyl tris(trimethylsilyl)silanes: substrates for Hiyama coupling

The oxidative treatment of vinyl tris(trimethylsilyl)silanes with hydrogen peroxide in aqueous sodium hydroxide in tetrahydrofuran generates reactive silanol or siloxane species that undergo Pd-catalyzed cross-couplings with aryl, heterocyclic, and alkenyl halides in the presence of Pd(PPh₃)₄ and tetrabutylammonium fluoride. Hydrogen peroxide and base are necessary for the coupling to occur while activation of the silanes with fluoride is not required. The conjugated and unconjugated tris(trimethylsilyl)silanes serve as good cross-coupling substrates. The (E)-silanes undergo coupling with retention of stereochemistry while coupling of (Z)-silanes occurred with lower stereoselectivity to produce an E/Z mixture of products.     

Synthesis of N-Z, N-Fmoc or Boc protected α-hydrazinoacids and study of the coupling reaction in solution of N-Z-α-hydrazinoesters

The preparation of chiral orthogonally protected N^α-Z, N^β-Fmoc- or Boc-α-hydrazinoacids derivatives, directly suitable for SPPS, is described in six steps with good yields starting from the corresponding α-aminoacids. The coupling reaction assays performed in liquid phase between N^α-Z-hydrazinoesters and N-Fmoc-α-aminoacids demonstrated the low reactivity of the hydrazinoester derivatives. However, we found that the acid fluoride method allowed the formation of hydrazinodipeptides almost quantitatively.     

Autoinductive exponential signal amplification: a diagnostic probe for direct detection of fluoride

A new example of an exponential signal amplification strategy for the direct detection of fluoride is demonstrated. The amplification occurred through reaction of fluoride with a responsive chromogenic probe. The probe activity is based on a unique dendritic chain reaction that generates a fluoride anion, which is the analyte of interest, during the disassembly pathway of the dendritic probe. This autoinductive amplification mechanism may be applied for detection of other analytes by coupling activity of a modified probe with that of the fluoride amplifier.     

氟离子对TiO2/膨润土光催化降解酸性桃红的影响

研究了在紫外光照射下, 添加氟离子对P25(锐钛矿)和TiO2/膨润土光催化降解酸性桃红(SRB)的影响. 紫外可见光谱测定结果表明无氟的反应体系, pH值越小, 光降解速率越快; pH值固定, 添加氟离子越多, 反应速率越快, 在TiO2/膨润土催化剂上, 当氟离子浓度达到一定程度时, 反应速率不再变化. 在P25和TiO2/膨润土催化剂上, 添加氟离子对H2O2的产生量影响不同, 通过电子顺磁共振(EPR)技术探测到了超氧自由基和羟基自由基, 这两个体系添加氟离子对其产生强度影响不同, 这可能是因为TiO2/膨润土催化剂为层状结构, BET 比表面积较大, 经XRD和TEM测试表明其晶粒直径约为57.9 nm. TiO2/膨润土催化剂连续循环使用11次, 光催化活性基本不变, 这个现象说明TiO2/膨润土催化剂既易于从分散体系中分离出来, 而且其稳定性也好, 它是一个有应用前途的催化剂.     

Preparation and synthetic applications of aryl tetraflates (ArOSO2CF2CF2H)

We have recently developed an improved synthetic route to 1,1,2,2-tetrafluoroethanesulfonic acid (HCF2CF2SO3H, TFESA) and explored the applications of this newly available superacid in catalysis. Low volatility, ease of handling, and a convenient 1H NMR handle make this acid an attractive alternative to triflic acid. TFESA can also be converted to several of its derivatives: anhydride, sulfonyl chloride, and sulfonyl fluoride, which provide a good entry point for the synthesis of aryl sulfonates. We prepared several aryl esters of 1,1,2,2-tetrafluoroethanesulfonic acid (aryl tetraflates) and showed that they can be used in a number of palladium-catalyzed coupling reactions (Suzuki, Heck, and Buchwald-Hartwig couplings). While the reactivity of tetraflates lies between that of triflates and chlorides, tetraflates appear to be more thermally stable. Additionally, the presence of a hydrogen atom in the tetraflate group facilitates monitoring of reactions and characterization of derivatives.     

Mechanistic investigations of cooperative catalysis in the enantioselective fluorination of epoxides

This report describes mechanistic studies of the (salen)Co- and amine-cocatalyzed enantioselective ring opening of epoxides by fluoride. The kinetics of the reaction, as determined by in situ (19)F NMR analysis, are characterized by apparent first-order dependence on (salen)Co. Substituent effects, nonlinear effects, and reactivity with a linked (salen)Co catalyst provide evidence for a rate-limiting, bimetallic ring-opening step. To account for these divergent data, we propose a mechanism wherein the active nucleophilic fluorine species is a cobalt fluoride that forms a resting-state dimer. Axial ligation of the amine cocatalyst to (salen)Co facilitates dimer dissociation and is the origin of the observed cooperativity. On the basis of these studies, we show that significant improvements in the rates, turnover numbers, and substrate scope of the fluoride ring-opening reactions can be realized through the use of a linked salen framework. Application of this catalyst system to a rapid (5 min) fluorination to generate the unlabeled analog of a known PET tracer, F-MISO, is reported.     

全氟甲基乙烯基醚和其它含氟单体乳液共聚合的竞聚率测定

分别通过气相色谱法测定了全氟甲基乙烯基醚 (PMVE)与偏氟乙烯 (VDF)以及PMVE与四氟乙烯(TFE)二元乳液共聚反应中的气相单体组成和共聚物组成 ,然后用非线性回归法 (RREVM )计算得TFE PMVE及VDF PMVE乳液共聚合反应的表观竞聚率分别为γTFE =3 89和γPMVE =0 0 5以及γVDF =1 0 6和γPMVE =0 11.结合已经测定的TFE VDF二元乳液共聚的表观竞聚率 ,计算了由VDF TFE PMVE三元乳液共聚合反应合成的共聚物组成 ,后者与由1 9F NMR实测的共聚物组成吻合     

A heteronuclear bidentate Lewis acid as a phosphorescent fluoride sensor

Reaction of dimesityl-1,8-naphthalenediylborate (1) with C6F5HgCl results in the formation of a B/Hg heteronuclear bidentate Lewis acid (2), which complexes fluoride to afford [2-mu2-F]-. Structural and photophysical studies carried out in solution and in the solid state indicate that 2 is a highly selective and sensitive phosphorescent fluoride sensor. The proximity of the two Lewis acidic sites enforced by the 1,8-naphthalenediyl backbone promotes fluoride anion chelation and is, therefore, responsible for the high binding constant. The interplay of conjugative and spin-orbit coupling effects mediated by the boron and mercury atoms, respectively, results in the phosphorescent signaling of fluoride binding. Remarkably, fluoride binding occurs in partially aqueous solutions and results in a drastic change of the phosphorescence observed when the solutions are frozen.     

Fluoroalkoxides as Molecular Precursors of Fluoride Materials by the Sol-Gel Process

Numerous works have reported the preparation of pure oxide materials using the sol-gel process. The purpose of this paper is to show that it is possible to obtain pure fluoride homometallic or heterometallic materials at room temperature by the hydrolysis of tailored molecular precursors.The work is focussed on alkaline-earth and lanthanide fluoroalkoxides ([M(OR)n]n where OR = fluoroalkoxo group) and the characterization of the final products of their hydrolysis. The molecular precursors were characterized by FT-Raman and the final powders by XRD and EDXRMA.The formation of these fluoride materials involves fluoride organic by-products. The reactivity of these organic compounds on various substrates in terms of surface modification has been studied.     

Reactivity and regioselectivity in Stille couplings of 3-substituted 2,4-dichloropyridines

The influence of substituents at C-3 of 2,4-dichloropyridines on their reactivity and regioselectivity in Pd-catalyzed cross-couplings is studied. As a model reaction, the (Ph₃P)₂PdCl₂-catalyzed Stille coupling between 2-furyl(tributyl)tin and pyridines is chosen. Increased electron-withdrawing ability of a substituent at the pyridine 3-position improves the overall reactivity. Absolute selectivity for coupling at C-2 is achieved with an amino group at C-3, and the selectivity is totally reversed when the amino group is exchanged for a nitro substituent.     

Fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate: a reagent for formation of interchain carboxylic anhydrides on self-assembled monolayers

In this paper, we report the reactivity of fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate (TFFH), a reagent for transformation of carboxylic acids into acid fluorides in solution, toward self-assembled monolayers (SAMs) of 16-mercaptohexadecanoic acid on gold. Contrary to the solution-based reactions, we found that only interchain carboxylic anhydrides (ICAs), not acid fluorides (AFs), were obtained at surfaces by the facile interchain reaction under most reaction conditions studied. AFs were found to be formed only when tetrabutylammonium fluoride, a reagent inducing fast decomposition of ICAs, was added to the reaction mixture. The reactivity of TFFH toward carboxylic acid-terminated SAMs was different from that of cyanuric fluoride, which has been reported previously (Langmuir 2005, 21, 11765-11772). This study provides more insight into the role of the proximity effect in SAM-based reactions as well as another approach to the formation of ICAs from carboxylic acid-terminated SAMs.     

Effects of polyoxometalate and fluoride on adsorption and photocatalytic degradation of organic dye X3B on TiO2: the difference in the production of reactive species

It has been reported that addition of polyoxometalates (POM) or fluoride anions into the TiO(2) dispersions can significantly enhance the photocatalytic degradation (PCD) of weakly adsorptive organic pollutants in water such as chlorophenol. In this work, however, contradictory effects of POM and fluoride were observed on the PCD of highly adsorptive substrate X3B, an anionic organic dye, under similar conditions. The total rate of X3B PCD, determined by total loss of X3B both in solution and on the catalyst surface, was increased in the presence of fluoride, but the rate was decreased in the presence of POM. In both cases, the dark adsorption of X3B on TiO(2) was greatly decreased, ascribed to competitive adsorption of POM or fluoride that reduces the positive charges on the catalyst surface. The spectral analysis and the kinetic study using tert-butyl alcohol as hydroxyl radical scavenger revealed that the PCD of X3B on naked TiO(2) was predominately initiated by direct hole transfer, whereas addition of POM or fluoride into the TiO(2) dispersions enhanced the degradation of X3B via hydroxyl radical pathway. It is proposed that the surface occupation of POM on TiO(2) accelerates the production of surface-bound hydroxyl radicals, due to enhanced charge separation, whereas the fluoride replacement of surface hydroxyl groups of TiO(2) increases the production of free hydroxyl radicals in solution, due to enhanced hole availability for water oxidation. Assume that the relative reactivity among various active follows the order of free hydroxyl radicals > subsurface holes > surface-bound hydroxyl radicals, the proposal could account for the observed effects of POM and fluoride on the PCD of both weakly and highly adsorptive organic substrates over TiO(2) such as chlorophenol and X3B.